Nefopam is a chiral drug that has been developed for the treatment of moderate to severe pain. Although nefopam is marketed as a racemic mixture, the enantiomers of the drug have been shown to exhibit different biological activities. In vitro and in vivo studies have shown that (+)-nefopam has more potent analgesic and dopamine, norepinephrine and serotonin-uptake inhibitory properties than (−)-nefopam. WO03/105832 discloses that nefopam has utility in the treatment of emesis and related conditions, with (+)-nefopam being the preferred enantiomer.
An efficient and reliable method for the preparation of the individual enantiomers of nefopam and nefopam analogues is desirable. As racemic nefopam is readily available, a classical resolution process, involving separation of diastereoisomeric salts by selective crystallisation may be suitable.
Blaschke et al, Arch. Pharm. (Weinheim) 320:341-347 (1987), discloses resolution of nefopam, using 1 molar equivalent of O,O-dibenzoyl-L-tartaric acid. The resolution proceeds via formation of the monotartrate salt.